Whether in an organism or in a dish, cells of the same type differentiate, grow, and respond to stimuli with a high degree of heterogeneity. The Fluidigm C1 is a powerful platform for exploring this diversity. Using microfluidics, the C1 can isolate, process, and profile individual cells for genomic analysis, amplifying very small amounts of mRNA from up to 96 individual cells in parallel. In addition, the workflow for processing amplified cDNA generated by the C1 system results in multiplexed libraries that can be sequenced on any of the five Illumina sequencers available in the Columbia Genome Center. The C1 is particularly useful for studying cell differentiation, identifying responses of single cells to specific perturbations, and drug screening. Itis available for use by members of the Columbia University community.

The Nanostring nCounter uses color-coded molecular barcodes that can be used to generate high-precision quantitation of hundreds of target molecules simultaneously across a sample set. It can be used for analysis of gene expression, single-cell gene expression, lncRNA expression, and leukemia fusion genes. It can also measure microRNA expression (both alone and in combination with mRNA expression), copy number variations, and in ChIP-String expression analysis.

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At the core of the Fluidigm C1 Single-Cell Auto Prep System is a 96-well plate containing microfluidics. After individual cells are isolated in their own wells, the device amplifies their cDNA for genome-wide gene expression profiling. Scientists at the Columbia Genome Center are developing methods for addressing the technical and analytical challenges of single-cell RNA sequencing, and have begun generating some exciting data.

Since the invention of the first microscope, a procession of new technologies has enabled scientists to study individual cells at increasingly fine levels of detail. The last two years have witnessed an important next stage in this evolution, with the arrival of the first devices for genetically profiling single cells on a genome-wide scale.

The first commercial product in this field is the Fluidigm C1 Single-Cell Auto Prep System, which uses microfluidics to isolate single cells and offers the ability to generate gene expression profiles for up to 96 cells at a time. But because of the novelty of the technology and the inherent difficulties of working with single cells, it has presented a number of technical challenges for researchers interested in exploring biology at this level.

Now, scientists at the JP Sulzberger Columbia Genome Center led by Assistant Professors Peter Sims and Yufeng Shen have developed an experimental and computational pipeline that optimizes the C1’s capabilities. And even as they work to solve some of the challenges that are inherent to single-cell research, their approach has begun generating some exciting data for studying genetics in a variety of cell types.